RESUMEN
Rheumatoid arthritis (RA) is a chronic inflammatory disease of autoimmune origin with many associated genetic traits, including genes related to the control of inflammation. The A20 protein, encoded by the TNFAIP3 gene, is a negative regulator of NF-kB mediated inflammation. Several single nucleotide variants (SNVs) of TNFAIP3 are associated with susceptibility to RA in different ethnic groups, none of which has been evaluated in Mexican patients. OBJECTIVE: To examine the possible association of eight TNFAIP3 SNVs in Mexican patients with RA. MATERIALS: We studied 471 patients with RA and 500 controls, as well as eight TNFAIP3 SNVs: including, rs10499194C/T, rs6920220G/A, and rs2230926T/G, which have been associated with RA in European or Asian patients, in addition to rs373421182G/C, rs139054966T/G, rs5029924C/T, rs59693083A/G and rs61593413T/A, not previously examined in RA. All SNVs were evaluated by means of an allelic discrimination assay using TaqMan probes. RESULTS: The allelic and genotypic frequencies of all SNVs examined were similar between cases and controls, and none of them was associated with RA under the allelic, codominant, dominant, and recessive models, as well as in haplotype combinations. CONCLUSION: Our data indicate that TNFAIP3 SNVs evaluated herein are not risk factors for RA in Mexican subjects.
Asunto(s)
Artritis Reumatoide , Predisposición Genética a la Enfermedad , Humanos , Polimorfismo de Nucleótido Simple/genética , Proteínas Nucleares/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas de Unión al ADN/genética , Estudios de Casos y Controles , Artritis Reumatoide/genética , Genotipo , Inflamación , Nucleótidos , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Gymnema sylvestre (GS) and berberine (BBR) are natural products that have demonstrated therapeutic potential for the management of obesity and its comorbidities, as effective and safe alternatives to synthetic drugs. Although their anti-obesogenic and antidiabetic properties have been widely studied, comparative research on their impact on the gene expression of adipokines, such as resistin (Res), omentin (Ome), visfatin (Vis) and apelin (Ap), has not been reported. METHODOLOGY: We performed a comparative study in 50 adult Mexican patients with obesity treated with GS or BBR for 3 months. The baseline and final biochemical parameters, body composition, blood pressure, gene expression of Res, Ome, Vis, and Ap, and safety parameters were evaluated. RESULTS: BBR significantly decreased (p < 0.05) body weight, blood pressure and Vis and Ap gene expression and increased Ome, while GS decreased fasting glucose and Res gene expression (p < 0.05). A comparative analysis of the final measurements revealed a lower gene expression of Ap and Vis (p < 0.05) in patients treated with BBR than in those treated with GS. The most frequent adverse effects in both groups were gastrointestinal symptoms, which attenuated during the first month of treatment. CONCLUSION: In patients with obesity, BBR has a better effect on body composition, blood pressure, and the gene expression of adipokines related to metabolic risk, while GS has a better effect on fasting glucose and adipokines related to insulin resistance, with minimal side effects.
Asunto(s)
Adipoquinas , Berberina , Composición Corporal , Gymnema sylvestre , Obesidad , Resistina , Humanos , Masculino , Femenino , Adulto , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Adipoquinas/sangre , Adipoquinas/metabolismo , Composición Corporal/efectos de los fármacos , Persona de Mediana Edad , Berberina/farmacología , Resistina/sangre , Resistina/metabolismo , Apelina , Presión Sanguínea/efectos de los fármacos , Nicotinamida Fosforribosiltransferasa/metabolismo , Citocinas/metabolismo , Citocinas/sangre , Extractos Vegetales/farmacología , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Lectinas , Proteínas Ligadas a GPI/metabolismo , Proteínas Ligadas a GPI/genética , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/uso terapéuticoRESUMEN
During the transition from a healthy state to a cancerous one, cells alter their metabolism to increase proliferation. The underlying metabolic alterations may be caused by a variety of different regulatory events on the transcriptional or post-transcriptional level whose identification contributes to the rational design of therapeutic targets. We present a mechanistic strategy capable of inferring enzymatic regulation from intracellular metabolome measurements that is independent of the actual mechanism of regulation. Here, enzyme activities are expressed by the space of all feasible kinetic constants (k-cone) such that the alteration between two phenotypes is given by their corresponding kinetic spaces. Deriving an expression for the transformation of the healthy to the cancer k-cone we identified putative regulated enzymes between the HeLa and HaCaT cell lines. We show that only a few enzymatic activities change between those two cell lines and that this regulation does not depend on gene transcription but is instead post-transcriptional. Here, we identify phosphofructokinase as the major driver of proliferation in HeLa cells and suggest an optional regulatory program, associated with oxidative stress, that affects the activity of the pentose phosphate pathway.